Accelerated superfractionated radiotherapy with concomitant boost for invasive bladder cancer (original) (raw)
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International Journal of Radiation Oncology*Biology*Physics, 2002
Purpose: A growing body of evidence supports the efficacy of accelerated superfractionated radiotherapy with concomitant boost for advanced head-and-neck carcinomas. This study represents a single-institution experience, performed to identify the factors influencing tumor control, survival, and toxicity. Methods and Materials: Between 1988 and 1999, 133 patients with primary squamous cell head-and-neck carcinoma underwent accelerated superfractionated radiotherapy using a concomitant boost. The concomitant boost in this regimen was delivered using reduced fields delivered 3 times weekly in a twice-daily schedule during the final phase. The total radiation dose ranged from 64.8 Gy to 76.5 Gy (mean 71.1). Patients were evaluated in follow-up for local control and late toxicity. Multivariate analysis of treatment and patient parameters was performed to evaluate their influence on toxicity, local control, and overall survival. Results: With a mean follow-up of 37 months, the actuarial overall survival rate for the entire group at 5 years was 24% and the local control rate was 57%. The tumor volume was the most significant predictor of local control, such that each 1-cm 3 increase in volume was associated with a 1% decrease in local control. For patients with tumor volumes <30 cm 3 vs. >30 cm 3 , the 5-year disease-specific survival rate was 52% and 27% (p ؍ 0.004) and locoregional control rate was 76% and 26% (p <0.001), respectively. Seventy-six patients with a minimum of 12 months and median of 39 months toxicity follow-up were studied for late effects. None of these patients experienced Grade 4 or 5 toxicity. The actuarial rate of significant toxicity (Grade III or greater) was 32% at 5 years. Of the toxicities observed, xerostomia (19%) was the most common. Multivariate analysis revealed N stage and dose as independent predictors of Grade 3 effects. Conclusion: The locoregional control and survival for patients in this institutional experience compare favorably to other published reports. Tumors of the larynx had the best prognosis. Larger volume tumors were associated with significantly lower local control and survival. Significant late effects were related to dose and nodal status.
International Journal of Radiation Oncology Biology Physics, 2000
Addition of thoracic radiation therapy (TRT) to chemotherapy (CHT) can increase overall survival in patients with small cell lung cancer limited-disease (SCLC-LD). Accelerated fractionation and early concurrent platinum-based CHT, in combination with prophylactic cranial irradiation, represent up-front treatment for this group of patients. Optimised and tailored local and systemic treatment is important. These concepts were applied when a new regional treatment programme was designed at Sahlgrenska University Hospital in 1997. The planned treatment consisted of six courses of CHT (carboplatin/etoposide)'TRT9prophylactic cranial irradiation (PCI). Standard TRT was prescribed as 1.5 Gy BID to a total of 60 Gy during 4 weeks, starting concomitantly with the second or third course of CHT. However, patients with large tumour burdens, poor general condition and/or poor lung function received 45 Gy, 1.5 Gy BID, during 3 weeks. PCI in 15 fractions to a total dose of 30 Gy was administered to all patients with complete remission (CR) and ''good'' partial remission (PR) at response evaluation. Eighty consecutive patients were treated between January 1998 and December 2004. Forty-six patients were given 60 Gy and 34 patients 45 Gy. Acute toxicity occurred as esophagitis grade III (RTOG/EORTC) in 16% and as pneumonitis grade I ÁII in10%. There were no differences in toxicity between the two groups. Three-and five-year overall survival was 25% and 16%, respectively. Median survival was 20.8 months with no significant difference between the two groups. In conclusion, TRT with a total dose of 60 or 45 Gy is feasible with comparable toxicity and no difference in local control or survival. Distant metastasis is the main cause of death in this disease; the future challenge is thus further improvement of the systemic therapy combined with optimised local TRT.
International Journal of Radiation Oncology*Biology*Physics, 2002
Purpose: To present our experience using a twice-daily radiotherapy (RT) technique, including hyperfractionated and accelerated-hyperfractionated RT, on nasopharyngeal carcinoma (NPC) patients. The dose to the primary tumor was increased in the hope that local control could be increased without the cost of increased late complications. We analyzed acute and late complications and local control and compared the results with the results of NPC patients treated during the same period using conventional once-daily RT. Methods and Materials: Between October 1991 and July 1998, 222 histologically confirmed, Stage M0, previously unirradiated NPC patients completed RT at our hospital. Most patients had American Joint Committee on Cancer (AJCC) 1992 Stage III and IV disease. Among them, 88 received altered fractionated, twice-daily RT; 76 patients received hyperfractionated RT and 12 accelerated-hyperfractionated RT. The remaining 134 patients received a conventional once-daily regimen. Hyperfractionated RT was delivered using 120 cGy b.i.d. separated by 6-h intervals throughout the course. For the accelerated-hyperfractionated patients, 160 cGy b.i.d. was given, also at 6-h intervals. The median dose in the twice-daily group was 7810 cGy (range 6840 -8200). In the once-daily regimen, RT was delivered using 180 -200 cGy q.d. The median tumor dose to the primary tumor was 7000 cGy (range 6560 -8100) given during about 8 weeks. The median follow-up time was 70.5 and 72 months for the twice-daily and once-daily groups, respectively. Results: The incidence of acute toxicities was higher in the twice-daily group with more severe mucositis and moist desquamation than in the once-daily group. Both groups had a similar incidence of late complications, except for 3 cases of temporal lobe necrosis in the twice-daily group, all in patients treated with 160 cGy. No difference was noted in recurrence-free local control between the two groups when the individual T stage was compared using AJCC 1992 or 1997 criteria (p ؍ 0.51 and 0.59, respectively). The 5-year local control rate for T1-3 (AJCC 1997) was 93.2% for the twice-daily group and 86.4% for the once-daily group (p ؍ 0.45). In Stage T4 (AJCC 1997) patients, the local control rate dropped drastically to 43.5% and 36.9% for the twice-daily and once-daily groups, respectively. The overall neck control rate at 5 years was 87.3% and 80.3% for the twice-daily and once-daily patients, respectively (p ؍ 0.16). The overall locoregional control rate was 82.7% for the twice-daily group and 66.6% for the once-daily group. The difference was again not statistically significant, but showed a tendency in favor of the twice-daily regimen (p ؍ 0.055). Locoregional failure occurred mainly in Stage T4 patients with central nervous invasion for whom local control was particularly poor, with a failure rate of about 60%. Conclusion: The present data suggest that NPC patients can be safely treated using a 120-cGy twice-daily program with a 6-h interval up to 8000 cGy. The accelerated-hyperfractionated technique is not recommended. A large discrepancy in local control between patients with T1-3 and T4 disease was noted. For T1-3 disease, an excellent local control rate >90% was achieved using the twice-daily regimen. In contrast, failure in the T4 patients was as high as 55% in the twice-daily group and reached 65% in the once-daily group. More rigorous treatment is needed using either additional dose escalation or other strategies for T4 NPC patients. With a dose escalation of 1000 cGy using 120-cGy twice-daily RT, a trend toward better locoregional control and diseasespecific survival was noted in the twice-daily group. Whether this difference was truly the result of an increased dose needs additional confirmation in studies with larger patient numbers.
1998 Bieri - Acta Oncol - Concomitant Boost Radiotherapy in Oropharynx Carcinomas.pdf
Fifty-five patients with resectable and unresectable oropharynx carcinomas were treated with concomitant boost radiotherapy. Forty-two of the patients (76%) had stages III-IV disease. Although none of the patients had undergone major surgery to the primary tumor, 11 had neck dissections prior to radiotherapy, and 19 (35%) received chemotherapy. The planned total tumor dose was 69.9 Gy, delivered over 5.5 weeks. During the last 3.5 weeks, a boost to the initial gross disease was delivered in 13 fractions of 1.5 Gy each, as a second daily fraction in a progressively accelerated schedule; the prescribed dose outside the boost volume thus was 50.4 Gy. Median follow-up for surviving patients was 31.5 months (range: 16-65 months). All patients but one completed the planned radiotherapy schedule. According to the RTOG scoring system, 48 patients (88%) presented with grades 3 -4 acute toxicity. The rate of grades 3 -4 late complications was 12%. At three years the actuarial locoregional control rate was 69.5% and overall survival was 60%. We conclude that this concomitant boost schedule is feasible and does not seem to be associated with an excess risk of late complications. Acute toxicity was higher in association with chemotherapy, but remained manageable. Although the oncological results appear encouraging, evaluation of the efficacy of concomitant boost schedules compared with conventionally fractionated irradiation with or without concomitant chemotherapy requires prospective randomized trials.
International Journal of Radiation Oncology*Biology*Physics, 1993
The feasibility of reducing overall treatment time by 2 weeks in the curative radiotherapeutic management of head and neck cancer patients is reported in a pilot trial of Hyperfractionated, Accelerated Radiotherapy with Dose Escalation (HARDE). This regimen prescribes 76 Gy in 5 weeks to definitive head and neck cancer patients, and 65 Gy in 5 weeks to high-risk postoperative patients. The linear quadratic model is used to compare predicted tumor cell kill with HARDE versus that expected with conventional fractionation (CF). Between January 1991 and March 1992, 40 head and neck cancer patients were treated with HARDE at the University of Wisconsin Comprehensive Cancer Center. Case-matched controls treated with CF were identified from patients treated at the same institution between 1980-1990, based on tumor site, stage, and extent of prior surgery. Individual patient treatment data (total dose, fraction size, overall time) rather than idealized schedule data from each group were analyzed using the linear quadratic model. Seventy-nine case-matched controls were identified for comparison with HARDE patients. The predicted increase in log cell kill for HARDE patients over case-matched controls was 1.5 and 1.3 logs, respectively, in the definitive and postoperative settings. This difference in log cell kill projects an improvement in locoregional tumor control for HARDE patients of between 10-25%. HARDE patients experience very brisk acute mucosal reactions and moderately prolonged mucosal healing, however, 91% have completed therapy without a treatment break. A 2-week reduction in overall treatment time for curative head and neck cancer patients is feasible while maintaining doses > 70 Gy. Based on radiobiologic predictions, such treatment intensification may significantly improve rates of locoregional tumor control. However, intensified acute mucosal reactions accompany such accelerated therapy.
Head & Neck Oncology, 2010
Introduction: This paper evaluates tumour control and toxicity especially in relation to swallowing dysfunction in those patients with locally advanced oropharyngeal squamous cell carcinoma who have undergone either primary chemo-radiation or post-operative parotid sparing IMRT. The TOM scoring system was used to assess dysphagia. Methods: All patients with locally advanced (stage 3/4) squamous cell oropharyngeal cancer and who required either primary or post-operative RT were identified. Toxicity was recorded prospectively. The TOM score (0-5 where 5 indicates that the patient is able to eat a normal diet and 0-2 varying degrees of enteral feeding dependency), weights and trismus was recorded immediately prior to and following radiotherapy. Results: 24 patients were identified between 1/2003 and 11/2007. Median weight loss during radiotherapy was 9 kg. All but one patient had a gastrostomy (RIG) tube inserted prophylactically. With a mean follow-up of 37.1 months, 62.5% of pts had a TOM score of 5, 12.5% scored 3, 8% scored and 17% scored 0-2. For those patients whose swallowing function did recover, it took on average 8.7 months. 15% patients experienced trismus secondary to radiotherapy. 2 year overall survival was 92% and disease specific survival 96%. Conclusion: Excellent disease control with intensified schedules of radiotherapy with IMRT has been achieved in this patient population. Intermediate toxicity is significant but with longer follow-up, dysphagia continues to improve with 75% of patients not requiring any form of enteral or oral supplementation.
International Journal of Radiation Oncology*Biology*Physics, 2003
Background and purpose: The aim of this report was to describe the incidence and prevalence of acute and late morbidity in the DAHANCA 6&7 multicentre randomised trial with accelerated radiotherapy for squamous cell carcinoma of the head and neck. Materials and methods: The DAHANCA 6&7 study included 1476 patients eligible for primary radiotherapy alone. Patients were randomised between five or six weekly fractions of conventional radiotherapy. The prescribed dose was 66-68 Gy in 33-34 fractions. All patients were seen weekly during treatment and at regular intervals after completion where detailed morbidity recording was done. Reports from 1468 patients were available for analysis of treatment related morbidity. Results: Accelerated radiotherapy caused a significant (p < 0.05) increase in the peak incidence of: use of analgesics (53% vs. 65%), dysphagia (35% vs. 45%), mucosal oedema (52% vs. 59%), and mucositis (33% vs. 53%). All acute reactions were reversible and healed within three months after radiotherapy. Loss of taste, xerostomia, and acute skin reaction was not different between the two groups. For all late endpoints except fibrosis and atrophy a decline in prevalence was observed in the years after radiotherapy, there was no significant difference between randomisation arms in any of the late endpoints. Conclusions: Six fractions per week, resulting in a one-week reduction in overall treatment time relative to conventional radiotherapy increased acute but not late morbidity. Since acceleration improves locoregional tumour control, the schedule represents a significant improvement of the therapeutic ratio for head and neck radiotherapy and might be close to the maximal gain possible with accelerated fractionation alone.
Oral Oncology, 2014
s u m m a r y Objectives: We previously described dose-escalated intensity-modulated radiotherapy (IMRT) in squamous cell cancer of the larynx/hypopharynx (SCCL/H) to offer improved locoregional control with a low incidence of toxicity at 2 years. We now present outcome and safety data at 5 years. Materials and methods: A sequential cohort Phase I/II trial design was used. Patients with SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Results: Between 09/2002 and 01/2008, 60 patients (29 DL1, 31 DL2) with stage III (41% DL1, 52% DL2) and stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 5.7 (1.0-10.2) years and for DL2 was 6.0 (0.3-8.4) years. Five-year local control rates (95% confidence interval) for DL1 and DL2, respectively, were 68% (50.6-85.4%) and 75% (58.9-91.1%), locoregional progression-free survival rates were 54% (35.6-72.4%) and 62.6% (44.8-80.4%), and overall survival was 61.9% (44.1-79.7) and 67.6 (51.1-84.1%). Five-year laryngeal preservation rates were 66.7% (37.4-87.9%) and 71.4% (44.4-85.8%), respectively. Cumulative toxicities reported were: one patient in DL1 and 2 in DL2 developed benign pharyngeal strictures. No other G3/4 toxicities were reported. Conclusions: Dose-escalated IMRT at DL2 achieves higher 5-year local control, larynx preservation and survival rates with acceptable late toxicity. Recruitment into a Cancer Research UK Phase III study (ART-DECO), with DL2 as the experimental arm, is ongoing.